Olmesartan for Hypertension.pptx

Optimizing HTN care
Role of Olmesartan
Ramzi Tabbalat, MD, FACC, FSCCT
Abdali Comprehensive Hypertension Center
(ACHC)
Abdali Hospital
24/5/2023

1X risk
2X
risk
Cardiovascular mortality risk for individuals aged 40-69 years: stroke-
Ischemic heart disease and other vascular diseases.
0
2
4
8
115/75 135/85 155/95 175/105
6
Systolic BP/Diastolic BP (mmHg)
4X
risk
8X
risk
*
Lewington et al. Lancet 2002;360:1903–13
Cardiovascular Mortality Risk Doubles with
Each 20/10 mmHg Increase in
Systolic/Diastolic BP

SBP Reductions as Little as 2 mm Hg
Reduce the Risk of CV Events by Up to 10%
Meta-analysis of 61 prospective, observational studies
1 million adults
12.7 million person-years
Lewington S et al. Lancet. 2002;360:1903-1913.
2 mm Hg
decrease in
mean SBP
10% reduction in
risk of stroke
mortality
7% reduction in risk
of ischemic heart
disease mortality

Olmesartan
 Olmesartan is an angiotensin Ⅱ type 1 receptor antagonist that inhibits action of
angiotensin Ⅱ on the Renin-Angiotensin-Aldosteron system (RAS) which plays a key role
in the Pathogenesis of HTN.
 It binds to the type 1 receptor with a high degree of insurmountability and with greater
affinity than most other ARBs.
 Rapidly and completely bioactivated during absorption from the GI tract.
 After oral administration, the peak plasma concentration (Cmax) of olmesartan is
reached after 1 to 2 hours. Food does not affect the its bioavailability.
 Approximately 35% to 50% of the absorbed dose is recovered in urine while the
remainder is eliminated in feces via the bile. No initial dosage adjustment is
recommended for elderly patients, for patients with moderate to marked renal
impairment (creatinine clearance ≤ 40ml/min) or with moderate to marked hepatic
dysfunction

ESC/ESH Guidelines 2018
Core drug treatment strategy for uncomplicated
HTN
Williams B, Mancia G, Spiering W, et al; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension.
Eur Heart J. 2018;39(33): 3021-104

Oletran
-Olmesartan Medoxomil Monotherapy

WIN OVER Study
• 8940 adults patients (>18 years) with essential hypertension as well as co-
morbidities such as angina, DM, or dyslipidemia.
• Olmesartan tablet 20 or 40 mg once daily for 6 months.
• Primary Outcome:
• The reduction of SBP to <140 mmHg and DBP to <90 mmHg at 3 and 6 months
from initiation of treatment.
•. 2014 May-Jun;66(3):340-4. doi: 10.1016/j.ihj.2014.05.002
Indian Heart J. 2014 May-Jun;66(3):340-4. doi: 10.1016/j.ihj.2014.05.002

WIN OVER Study
Results
Reduction in SBP Reduction in DBP
(P < 0.0001)

WIN OVER Study
Results
Responders for SBP Responders for DBP

WIN OVER Study
Conclusion
 Omlesartan 20/40 is effective in the reduction both Systolic and Diastolic BP
from Day 15 to Month 6.
 The percentage of responders for both systolic and diastolic blood pressure
increased consistently from day 15 to month 6.
 No serious adverse event was reported in the study.

OLMEBEST Study
• 823 adult patients aged 18-75 years with mild to moderate essential
HTN.
• Open-label olmesartan 20mg once daily for 8 weeks.
• At the end of this period, patients whose BP had not normalised* were
randomised to:
• Olmesartan monotherapy (40mg once daily, n = 302), or
• Olmesartan (20mg once daily)/hydrochlorothiazide (12.5mg once daily) combination therapy
(n = 325)
• Primary Outcome at 12 weeks: change in mean sitting DBP.
American Journal of Hypertension, Volume 18, Issue S4, May 2005, Page 87A, https://doi.org/10.1016/j.amjhyper.2005.03.242
*Normalisers were defined as patients whose DBP was <90 mmHg after 8 weeks

OLMEBEST Study
 For patients who did not achieve adequate BP control after initial treatment
with olmesartan 20 mg/day, olmesartan dose titration to 40 mg/day or addition
of hydrochlorothiazide (12.5 mg/day) elicited a sitting DBP response in the
majority of patients who had failed to respond to low-dose monotherapy, and
normalisation of sitting DBP in approximately 50% of patients
 Both these strategies represent effective and well tolerated treatment options
in patients who show an inadequate response to low-dose monotherapy with
olmesartan
American Journal of Hypertension, Volume 18, Issue S4, May 2005, Page 87A, https://doi.org/10.1016/j.amjhyper.2005.03.242
Results:

Efficacy in angiotensin receptor blockade: a
comparative review of data with olmesartan
Meta-analysis of studies involving ARBs, looking at the effect upon ABPM made
over 24 hours, daytime, night-time and the last 4–6 hours of the dosing interval.
Redon J, Fabia MJ. Efficacy in angiotensin receptor blockade: a comparative review of data with olmesartan.
J Renin Angiotensin Aldosterone Syst. 2009;10(3):147-56.

Mean changes in systolic and diastolic blood pressure (SBP; DBP) assessed by ambulatory blood
pressure monitoring over (a) 24 hours (b) the last four hours of the dosing interval.

Conclusion:
Significantly greater DBP and/or SBP reduction with Olmesartan over 24 Hours and
during the Final 4 hours of Treatment compared to other ARBs.
Olmesartan medox-omil, was consistently associated with a high level of
antihypertensive efficacy, both in terms of BP reductions assessed using
standard clinic measurements and using ABPM measurements.
Olmesartan might possess a greater degree of antihypertensive activity than other
ARBs at standard doses.

Blood pressure-lowering efficacy of olmesartan
relative to other angiotensin II receptor
antagonists: an overview of randomized controlled
studies
• A review of published studies investigating the dose-related efficacy on BP of
olmesartan and of other commercially available ARBs.
• All studies were prospective, multicenter, randomized, double-blind,
placebo-controlled parallel-group design, and conducted in
hypertensive adult patients, over 18 years of age (7280 patients, of
which 5769 received an ARB and 1511 received placebo).
• The treatment period was of 8 weeks, to ensure that most of the effect
of the drug was achieved.
• Efficacy assessment was based on the reduction of seated or supine
BP in mmHg at trough.
Zannad F, Fay R. Blood pressure-lowering efficacy of olmesartan relative to other angiotensin II receptor antagonists: an overview of randomized
controlled studies. Fundam Clin Pharmacol. 2007;21(2):181-90.

relative to other angiotensin II receptor antagonists:
an overview of randomized controlled studies
Changes from baseline in casual systolic blood pressure in
comparative studies. *P < 0.05 vs. olmesartan
Changes from baseline in casual diastolic blood pressure
in comparative studies. *P < 0.05 vs. olmesartan

relative to other angiotensin II receptor
antagonists: an overview of randomized controlled
studies
Conclusion:
 BP-lowering efficacy of olmesartan, defined as the maximal BP decrease
observed at the plateau of dose–effect relationships is at the highest end of
the range of efficacy compared with that of losartan, irbesartan, valsartan, and
candesartan.
 Among the studied ARBs, olmesartan can reduce DBP and SBP significantly
more than other ARBs.
 Differences in efficacy between antihypertensive agents do exist and are most
likely to be clinically meaningful, considering the relevance of optimal BP
control.

Antihypertensive efficacy of olmesartan and
candesartan assessed by 24-hour ABPM in
patients with essential HTN
• Randomised, double-blind, parallel-group study conducted
at 44 centres in Germany, Poland and the Czech
Republic.
• 643 patients (aged 19-86 years) with mainly mild-to-
moderate essential hypertension.
• Following a 2-week placebo run-in, eligible patients were
randomly assigned to receive olmesartan medoxomil
20mg (n = 319) or candesartan cilexetil 8mg (n = 324)
once daily for 8 weeks.
• Main outcome: changes in 24-h ABPM after 1, 2 and 8
weeks
Brunner H. et al. Clin Drug Investig. 2003;23(7):419-30. doi: 10.2165/00044011-200323070-00001

Results:
(a) Daytime systolic BP, * p = 0.0441, ** p = 0.0243, *** p = 0.0055
(b) (b) 24-hour diastolic BP, * p = 0.0143, ** p = 0.0055, *** p = 0.0004
(c) 24-hour systolic BP, * p = 0.0159, ** p = 0.0071;
(d) night-time diastolic BP, * p =0.0154;
(e) night-time systolic BP, * p = 0.0131.

 Olmesartan medoxomil reduced daytime and 24-hour DBP
and SBP, assessed by ABPM, more effectively than
candesartan cilexetil at the doses tested.
 The majority of the treatment effect in both groups was
seen after only 1 or 2 weeks of dosing, when the between-
group differences were already statistically significant.
 Both treatments were well tolerated
Conclusion:

Oletran Plus
-Olmesartan/Hydrochlorothiazide

Olmesartan medoxomil combined with
hydrochlorothiazide for the treatment of
hypertension
 Study Design:
An indirect comparison through a meta-analysis of randomized,
double-blind, controlled trials assessing cuff BP in hypertensive
patients with a DBP of 95– 115mmHg.
 Primary Outcome:
• Absolute Response Rate for Olmesartan/HCT comparing to
other ARB’s/HCT Combination at starting doses.
• Response Rate defined as DBP ≤ 90 or decrease from Baseline
of ≥10 mmHg.
Greathouse M. Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension. Vasc Health
Risk Manag. 2006;2(4):401-9.

hypertension
Antihypertensive efficacy of other angiotensin II receptor blocker/HCTZ combinations based on indirect
comparison through a meta-analysis of randomized, double-blind, controlled trials assessing cuff BP in
hypertensive patients with a DBP of 95–115 mmHg
Risk Manag. 2006;2(4):401-9.

hypertension
Conclusion:
Olmesartan/HCT Response rate in term of mean absolute
reduction from baseline (mmHg) in DBP and SBP are better
than Candesartan/HCT, losartan/HCT, Valsartan/HCT and
Irbesartan/HCT.
Risk Manag. 2006;2(4):401-9.

• Randomized, double-blind, factorial design study.
• After a placebo run-in period, eligible patients (n = 502) with a
baseline mean seated DBP (SeDBP) of 100 to 115 mm Hg
were randomized to one of 12 groups:
• Placebo, olmesartan medoxomil monotherapy (10, 20, or 40 mg/day, or
• HCTZ monotherapy (12.5 or 25 mg/day), or
• One of six groups of olmesartan medoxomil/HCTZ combination therapy.
• The primary endpoint was the change in mean trough SeDBP
from baseline at week 8.
Evaluation of antihypertensive therapy with the
combination of olmesartan and
hydrochlorothiazide
Study Design:
American Journal of Hypertension, Volume 17, Issue 3, March 2004, Pages 252–259,
https://doi.org/10.1016/j.amjhyper.2003.11.003

hydrochlorothiazide
Results:

 Olmesartan medoxomil plus HCTZ produced greater reductions in both
SeDBP and seated systolic blood pressure (SeSBP) at week 8 than did
monotherapy with either component.
 All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP
and SeSBP compared with placebo in a dose-dependent manner.
 The result indicated that olmesartan/HCTZ 40/25 mg combination achieved
the greatest reduction, and the highest responder rate (92.3%) and control
rates (79.5% for diastolic and 87.2% for systolic)
 All dosages of monotherapy and combination therapy were safe and well
tolerated, and no significant incidence of treatment-emergent adverse effects
was reported
hydrochlorothiazide
Conclusion:

Combitran
-Olmesartan/Amlodipine

Clinical Efficacy and Safety of Combination
Therapy with Amlodipine and Olmesartan
• A prospective, open-label, and multicenter trial in China
• Patients were initially treated with OLM 20 mg/d combined
with AML 5 mg/d for 8 wks. Then OLM was uptitrated to 40
mg/d or changed to an OLM/HCTZ (20/12.5 mg/d)
compound if the patients did not reach the target of seated
diastolic BP <90 mm Hg (<80 mm Hg in patients with
diabetes) after 8 weeks.
Gao P, Mei K, Li H, et al. Clinical Efficacy and Safety of Combination Therapy with Amlodipine and Olmesartan or an Olmesartan/Hydrochlorothiazide
Compound for Hypertension: A Prospective, Open-Label, and Multicenter Clinical Trial in China. Curr Ther Res Clin Exp. 2015;90:99-105.

Conclusion:
 The overall response rate of the combination therapy was
59.2% (95% CI, 54.23%-63.97%) at Week 2 and gradually
increased to 97.1% (95% CI, 94.93%-98.47%) at the end of the
study (Week 16)
 The combination therapy with OLM or OLM/HCTZ was well
tolerated

COACH: The combination of olmesartan
and amlodipine in controlling high BP
 Multicenter, randomized, double-blind, placebo-controlled,
factorial study.
 Patients who were naive to antihypertensive therapy or who
underwent a washout of previous antihypertensive therapy for up
to 2 weeks and had a seated diastolic BP (SeDBP) of 95 to 120 mm
Hg were randomized to receive 1 of the following for 8 weeks: OM
10, 20, or 40 mg; amlodipine (AML) 5 or 10 mg; each possible
combination of OM and AML; or placebo.
 Objective: The aim of this study was to compare the efficacy and
tolerability of combinations of olmesartan medoxomil (OM) and
amlodipine besylate with those of the component monotherapies
in patients with mild to severe hypertension.
Clin Ther. 2008 Apr;30(4):587-604. doi: 10.1016/j.clinthera.2008.04.002

 Conclusion:
 The antihypertensive effects of AML+OM±HCTZ regimens were well maintained
during the 44-week follow-up period in all three patient subgroups whose
hypertension is generally considered difficult-to-treat.
 Importantly, titration to higher dosages of OM+AML, and the addition of HCTZ,
resulted in greater SeBP reductions with each titration step.
 The regimen of multiple hypertensive therapies with differing mechanisms of
action provides additive benefit in BP control and achievement of guideline-
recommended BP goals without compromising patient safety.

Combitran Plus
Olmesartan/Amlodipine/Hydrochlorothiazide

 Study Design:
• Multicenter, randomized, double-blind, parallel-group study in patients aged ≥ 18
years who had a mean seated BP ≥140/100 mm Hg or ≥160/90 mm Hg.
• Triple combination treatment with OM 40 mg + AML 10 mg + HCTZ 25 mg was
compared with dual combinations of the individual components
• OM 40 mg/AML 10 mg in fixed-dose combination
• OM 40 mg/HCTZ 25 mg in fixed-dose combination, and
• AML 10 mg + HCTZ 25 mg
• Objective: The aim of this study was to determine whether a triple combination of
OM, AML, and HCTZ had a clinically significant benefit compared with dual
combinations of the individual components in patients with moderate to severe
hypertension.
TRINITY: Triple therapy with olmesartan ,
amlodipine, and HCTZ in adult patients with
hypertension
Clinical Therapeutics. Volume 32, Issue 7, July 2010, Pages 1252-1269

hypertension
The change in seated diastolic BP (SeDBP) from baseline to week 12;
SeDBP reduction of ≥2 mm Hg was considered a clinically significant
benefit.

In this population of adult patients with moderate to severe HTN, triple
combination Rx with OM 40 mg + AML 10 mg + HCTZ 25 mg was associated
with significant BP reductions compared with dual combinations of the
individual components. The reductions in BP translated into a greater % of
patients achieving the BP goal. All treatments were generally well tolerated.
hypertension

Olmesartan Extra Organ Protection
 Effect on DM Type 2
 Effect on Progression of Coronary Atherosclerosis
 Effect on Vessel Remodelling
 Effect on Stroke
 Anti-Inflammatory effect of Olmesartan
 Effect on Migraine
 Effect on Hyperlipidaemia
 Effect on LVMI

ROADMAP: Olmesartan for the Delay or
Prevention of Microalbuminuria in Type 2
Diabetes
 Study Design:
Randomized, double-blind, multicenter, controlled trial
4447 patients with type 2 diabetes received olmesartan 40 mg or placebo for a
median of 3.2 years.
The time to the first onset of microalbuminuria.
The times to the onset of renal and cardiovascular events were analyzed as
secondary end points.
N Engl J Med 2011;364:907-17

Diabetes
Occurrence of Microalbuminuria during the 48-Month Follow-up in the Two Study Groups
N Engl J Med 2011;364:907-17

Conclusion:
 The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the
patients taking olmesartan and 71% taking placebo; blood pressure measured
in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the
placebo group.
 the time to the onset of microalbuminuria was increased by 23% with
olmesartan.
Diabetes
N Engl J Med 2011;364:907-17

 Study Design
 Serial volumetric IVUS examinations (baseline and 14 months) were performed in
247 patients with SAP.
 Patients were randomly assigned to receive 20–40mg of Olmesartan or control,
and treated with a combination of β-blockers, calcium channel blockers, diuretics,
nitrates, glycemic control agents and/or statins per physician's guidance.
 Three-year clinical outcomes and annual progression rate of atherosclerosis,
assessed by serial volumetric IVUS (mean lengths; 43mm
(J Am Coll Cardiol 2010;55:976–82
OLIVUS: Effect on Progression of
Coronary Atherosclerosis

Representative Serial Volumetric IVUS Analysis in
the Control Group

OLIVUS study: impact of olmesartan on
progression of coronary atherosclerosis
Hiroata A et al. J Am Coll Cardiol 2010; 55(10): 976-982

 Results
 These observations suggest a positive role in a potentially lower rate of coronary
atheroma progression through the administration of Olmesartan, an angiotensin-II
receptor blocking agent, for patients with stable angina pectoris.

Benefits of olmesartan in controlling HTN and
cerebral hemodynamics after stroke
 Study Design:
• Compare the effects of the ARB olmesartan and the CCB amlodipine on
cerebral hemodynamics in hypertensive patients with a history of stroke.
• ABPM was used to measure BP, and xenon-computed tomography (Xe-
CT) to measure CBF and cerebrovascular reserve capacity (CRC) in both
the affected and unaffected hemispheres.
• Rehabilitation outcomes were also evaluated.
Matsumoto, S., Shimodozono, M., Miyata, R. et al. Benefits of the angiotensin II receptor antagonist olmesartan in controlling
hypertension and cerebral hemodynamics after stroke. Hypertens Res 32, 1015–1021 (2009). https://doi.org/10.1038/hr.2009.143

Mean hourly systolic blood pressure (SBP) and diastolic blood pressure (DBP) from ambulatory BP monitoring before (•) and
after 4 (Δ) and 8 (○) weeks’ treatment with olmesartan or amlodipine.

Cerebrovascular reserve capacity (CRC) before and after treatment. Circles with bars
represent means±s.d. Only the increase in CRC observed on the affected side of the
brain in the Olmesartan group was statistically significant (*P<0.01 vs. baseline).
Cerebral blood flow (CBF) before and after treatment. Upper panels show CBF on the
affected side of the brain and the lower panels show CBF on the unaffected side. Circles
with bars represent means±s.d. Increases in CBF observed in both the affected and
unaffected sides of the brain were statistically significant (*P<0.01 vs. baseline) in the
Olmesartan group.

Conclusion:
 This study has shown that treating hypertensive stroke patients for 8
weeks with olmesartan, but not amlodipine, increased CBF in the
affected and unaffected hemispheres, increased CRC in the affected
hemisphere, and improved rehabilitation outcomes, despite both drugs
achieving comparable reductions in BP

Take Home Messages:
 Olmesartan efficacy is the Highest end of the range of efficacy of ARBs, with
better BP reduction alone and in Combination.
 Sustained 24-hour BP Control that remains in the last 4 hours of the day
dosing period.
 Organ Protections benefits beyond BP Lowering Effect:
 Secondary Stroke Prevention and Improved rehabilitation
 Delay onset of Microalbuminuria by 23 % in DM 2 Patient
 Reduction Lipid profile specially TG
 Decrease LVMI which increase risk of CVD Comorbidities in HTN Patients.

Patients Profile
1- Naïve Patient with different Severity of HTN
2- HTN Patient with fluctuations in BP Measurements during the Day.
3- HTN Patients not controlled to other ARBs and ACEIs.
4- HTN Patient with Previous Stroke.
5- HTN Patient DM Type 2
6- HTN Patient with Elevated TG.
7- HTN Patient with any Comorbidity that increase LVMI ( AF, CKD….) which increase
risk of CVD incident and mortality.
8- HTN Patient on candesartan: Better Efficacy, More reduction of TG, More reduction
on LVM

Olmesartan for Hypertension.pptx

Recommended

Recommended

More Related Content

Similar to Olmesartan for Hypertension.pptx

Similar to Olmesartan for Hypertension.pptx (20)

Recently uploaded

Recently uploaded (20)

Olmesartan for Hypertension.pptx

Editor's Notes